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MyoD induced enhancer RNA interacts with hnRNPL to activate target gene transcription during myogenic differentiation.

ABSTRACT: Emerging evidence supports roles of enhancer RNAs (eRNAs) in regulating target gene. Here, we study eRNA regulation and function during skeletal myoblast differentiation. We provide a panoramic view of enhancer transcription and categorization of eRNAs. Master transcription factor MyoD is crucial in activating eRNA production. Super enhancer (se) generated seRNA-1 and -2 promote myogenic differentiation in vitro and in vivo. seRNA-1 regulates expression levels of two nearby genes, myoglobin (Mb) and apolipoprotein L6 (Apol6), by binding to heterogeneous nuclear ribonucleoprotein L (hnRNPL). A CAAA tract on seRNA-1 is essential in mediating seRNA-1/hnRNPL binding and function. Disruption of seRNA-1-hnRNPL interaction attenuates Pol II and H3K36me3 deposition at the Mb locus, in coincidence with the reduction of its transcription. Furthermore, analyses of hnRNPL binding transcriptome-wide reveal its association with eRNAs is a general phenomenon in multiple cells. Collectively, we propose that eRNA-hnRNPL interaction represents a mechanism contributing to target mRNA activation.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC6923398 | biostudies-literature |

REPOSITORIES: biostudies-literature

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MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation

Project description:Evidence of widespread transcription at active enhancers became apparent. However, our understanding about the functions of enhancer RNAs (eRNAs) and their mechanistic roles remains incomplete. Here, we study eRNA regulation and function using skeletal myoblast differentiation as a paradigm. We provide a panoramic view of enhancer transcription and uncover reprogramming in enhancer transcription occurring during myogenic differentiation. We demonstrate the critical role of MyoD in activating eRNAs production. Results from in depth dissection of two eRNAs transcribed from super enhancers (seRNA-1 and -2) suggest that seRNAs can promote myogenic differentiation in vitro and in vivo; the induction of the seRNAs is in coordination with the activation of the neighboring genes and seRNA loss largely impairs their expression. Mechanistically, we elucidate these seRNAs specifically bind to heterogeneous nuclear ribonucleoprotein L (hnRNPL) and modulate hnRNPL binding to the target promoter. A CAAA tract on the seRNA was identified to be essential in mediating the interaction between seRNA-1 and hnRNPL. Disruption of seRNA-hnRNPL interaction attenuates Pol II and H3K36me3 deposition at the target genes, in coincidence with the reduction of their expression. Furthermore, analyses of hnRNPL binding transcriptome-wide reveals its association with eRNAs is a general phenomenon in multiple cells. Collectively, we propose that eRNA-hnRNPL interaction contributes to target mRNA activation.

2019-10-03 | GSE114659 | GEO

MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [RNA-Seq]

2019-10-03 | GSE114658 | GEO

MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [GRO-Seq]

2019-10-03 | GSE114657 | GEO

MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [CLIP-Seq]

2019-10-03 | GSE114656 | GEO

MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation

Project description:MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation

| PRJNA472068 | ENA

MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [RNA-Seq]

Project description:MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [RNA-Seq]

| PRJNA472071 | ENA

MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [GRO-Seq]

Project description:MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [GRO-Seq]

| PRJNA472072 | ENA

MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [CLIP-Seq]

Project description:MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation [CLIP-Seq]

| PRJNA472070 | ENA

MyoD- and FoxO3-mediated hotspot interaction orchestrates super-enhancer activity during myogenic differentiation.

Project description:Super-enhancers (SEs) are cis-regulatory elements enriching lineage specific key transcription factors (TFs) to form hotspots. A paucity of identification and functional dissection promoted us to investigate SEs during myoblast differentiation. ChIP-seq analysis of histone marks leads to the uncovering of SEs which remodel progressively during the course of differentiation. Further analyses of TF ChIP-seq enable the definition of SE hotspots co-bound by the master TF, MyoD and other TFs, among which we perform in-depth dissection for MyoD/FoxO3 interaction in driving the hotspots formation and SE activation. Furthermore, using Myogenin as a model locus, we elucidate the hierarchical and complex interactions among hotspots during the differentiation, demonstrating SE function is propelled by the physical and functional cooperation among hotspots. Finally, we show MyoD and FoxO3 are key in orchestrating the Myogenin hotspots interaction and activation. Altogether our results identify muscle-specific SEs and provide mechanistic insights into the functionality of SE.

| S-EPMC5587775 | biostudies-literature

Long non-coding RNA Linc-RAM enhances myogenic differentiation by interacting with MyoD.

Project description:Long non-coding RNAs (lncRNAs) are important regulators of diverse biological processes. Here we report on functional identification and characterization of a novel long intergenic non-coding RNA with MyoD-regulated and skeletal muscle-restricted expression that promotes the activation of the myogenic program, and is therefore termed Linc-RAM (Linc-RNA Activator of Myogenesis). Linc-RAM is transcribed from an intergenic region of myogenic cells and its expression is upregulated during myogenesis. Notably, in vivo functional studies show that Linc-RAM knockout mice display impaired muscle regeneration due to the differentiation defect of satellite cells. Mechanistically, Linc-RAM regulates expression of myogenic genes by directly binding MyoD, which in turn promotes the assembly of the MyoD-Baf60c-Brg1 complex on the regulatory elements of target genes. Collectively, our findings reveal the functional role and molecular mechanism of a lineage-specific Linc-RAM as a regulatory lncRNA required for tissues-specific chromatin remodelling and gene expression.

| S-EPMC5241866 | biostudies-literature

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